Clinical Outcome After Endovascular Treatment in Patients With Active Cancer and Ischemic Stroke: A MR CLEAN Registry Substudy

Objective:To explore clinical and safety outcomes of patients with acute ischemic stroke (AIS) and active cancer after endovascular treatment (EVT).Methods:Using data from the MR CLEAN Registry, we compared patients with active cancer (defined as cancer diagnosed within 12 months prior to stroke, metastatic disease, or current cancer treatment) to patients without cancer. Outcomes were 90-day modified Rankin Scale (mRS) score, mortality, successful reperfusion (eTICI scores≥2b), symptomatic intracranial hemorrhage (sICH), and recurrent stroke. Subgroup analyses were performed in patients with a pre-stroke mRS score of 0 or 1 and according to treatment setting (curative or palliative). Analyses were adjusted for prognostic variables.Results:Of 2583 patients who underwent EVT, 124 (4.8%) had active cancer. They more often had pre-stroke disability (mRS≥2: 34.1% vs. 16.6%). The treatment setting was palliative in 25.3% of the patients. There was a shift towards worse functional outcome at 90 days in patients with active cancer (adjusted common OR 2.2, 95% CI 1.5-3.2). At 90 days, patients with active cancer were less often independent (mRS 0-2: 22.6% vs. 42.0%, aOR 0.5, 95% CI 0.3-0.8), and more often dead (52.2% vs. 26.5%, aOR 3.2, 95% CI 2.1-4.9). Successful reperfusion (67.8% vs. 60.5%, aOR 1.4, 95% CI 1.0-2.1) and sICH rates (6.5% vs. 5.9%, aOR 1.1, 95 %CI 0.5-2.3) did not differ. Recurrent stroke within 90 days was more common in patients with active cancer (4.0% vs. 1.3%, aOR 3.1, 95% CI 1.2-8.1). The sensitivity analysis of patients with a pre-stroke mRS of 0 or 1 showed that patients with active cancer still had a worse outcome at 90 days (acOR 1.9, 95% CI 1.2-3.0). Patients with active cancer in a palliative treatment setting regained functional independence less often compared to patients in a curative setting (18.2% vs. 32.1%) and mortality was also higher (81.8% vs. 39.3%).Conclusions:Despite similar technical success, patients with active cancer had significantly worse outcomes after EVT for AIS. Moreover, they had an increased risk of recurrent stroke. Nevertheless, about a quarter of the patients regained functional independence and the risk of other complications, most notably sICH, was not increased.Classification of Evidence:This study provides Class I evidence that patients with active cancer undergoing EVT for AIS have worse functional outcomes at 90 days compared to those without active cancer.

Machine Learning to Calculate Heparin Dose in COVID-19 Patients with Active Cancer

To realize a machine learning (ML) model to estimate the dose of low molecular weight heparin to be administered, preventing thromboembolism events in COVID-19 patients with active cancer. Methods: We used a dataset comprising 131 patients with active cancer and COVID-19. We considered five ML models: logistic regression, decision tree, random forest, support vector machine and Gaussian naive Bayes. We decided to implement the logistic regression model for our study. A model with 19 variables was analyzed. Data were randomly split into training (70%) and testing (30%) sets. Model performance was assessed by confusion matrix metrics on the testing data for each model as positive predictive value, sensitivity and F1-score. Results: We showed that the five selected models outperformed classical statistical methods of predictive validity and logistic regression was the most effective, being able to classify with an accuracy of 81%. The most relevant result was finding a patient-proof where python function was able to obtain the exact dose of low weight molecular heparin to be administered and thereby to prevent the occurrence of VTE. Conclusions: The world of machine learning and artificial intelligence is constantly developing. The identification of a specific LMWH dose for preventing VTE in very high-risk populations, such as the COVID-19 and active cancer population, might improve with the use of new training ML-based algorithms. Larger studies are needed to confirm our exploratory results.

The Role of Factor Xa-Independent Pathway and Anticoagulant Therapies in Cancer-Related Stroke

Background: The optimal strategy for stroke prevention in cancer patients is unknown. We compared the underlying mechanisms of coagulopathy and the effects of anticoagulants in patients with active cancer and atrial fibrillation (AF). Methods: We retrospectively enrolled 46 consecutive patients with embolic stroke of unknown source and active cancer (cancer stroke). We consecutively screened patients with cancer patients without stroke (n = 29), AF stroke (n = 52), and healthy subjects (n = 28), which served as controls. Patients with cancer stroke were treated with either enoxaparin (a low-molecular-weight heparin) or a factor Xa inhibitor, and those with AF stroke were treated with factor Xa inhibitors. D-dimer, factor Xa, and circulating cell-free DNA (cfDNA), a marker of neutrophil extracellular traposis, were measured at both before and after anticoagulation. Results: In AF stroke, factor Xa activity and cfDNA and D-dimer levels were decreased by treatment with factor Xa inhibitors. In contrast, in cancer stroke, factor Xa activity was decreased, D-dimer levels were unchanged, and cfDNA levels were increased by treatment with factor Xa inhibitors. In cancer stroke patients treated with enoxaparin, D-dimer levels were decreased (p = 0.011) and cfDNA levels were unchanged. Conclusion: The anticoagulation effects of factor Xa inhibitors differed between cancer stroke and AF stroke.

Clinical Management of COVID-19 in Cancer Patients with the STAT3 Inhibitor Silibinin

COVID-19 pathophysiology is caused by a cascade of respiratory and multiorgan failures arising, at least in part, from the SARS-CoV-2-driven dysregulation of the master transcriptional factor STAT3. Pharmacological correction of STAT3 over-stimulation, which is at the root of acute respiratory distress syndrome (ARDS) and coagulopathy/thrombosis events, should be considered for treatment of severe COVID-19. In this perspective, we first review the current body of knowledge on the role of STAT3 in the pathogenesis of severe COVID-19. We then exemplify the potential clinical value of treating COVID-19 disease with STAT3 inhibitors by presenting the outcomes of two hospitalized patients with active cancer and COVID-19 receiving oral Legalon®—a nutraceutical containing the naturally occurring STAT3 inhibitor silibinin. Both patients, which were recruited to the clinical trial SIL-COVID19 (EudraCT number: 2020-001794-77) had SARS-CoV-2 bilateral interstitial pneumonia and a high COVID-GRAM score, and showed systemic proinflammatory responses in terms of lymphocytopenia and hypoalbuminemia. Both patients were predicted to be at high risk of critical COVID-19 illness in terms of intensive care unit admission, invasive ventilation, or death. In addition to physician’s choice of best available therapy or supportive care, patients received 1050 mg/day Legalon® for 10 days without side-effects. Silibinin-treated cancer/COVID-19+ patients required only minimal oxygen support (2–4 L/min) during the episode, exhibited a sharp decline of the STAT3-regulated C-reactive protein, and demonstrated complete resolution of the pulmonary lesions. These findings might inspire future research to advance our knowledge and improve silibinin-based clinical interventions aimed to target STAT3-driven COVID-19 pathophysiology.

Early and Long Term Results of Our Open Heart Surgical Operations in the Presence of Active Oncological Diseases

Objectives: Active cancer and heart disease, which share similar environmental and biological characteristics, can occur concomitantly. Open heart surgery may be required for these patients when indicated. The aim of this study is to demonstrate the early and long-term results and discuss the intervention strategy in patients with different types of active malignancies, who underwent open heart surgery. Patients and Methods: Between January 2012 and May 2020, open heart surgery was performed on 10 patients with active malignancies. The mean age was 65.5 (52–77), and 4 of the patients were female. 2 patients were operated emergently due to advanced pleural effusion. AVR+CABG, CABG, CABG+left upper lobectomy and AVR+MVR were performed in 4 patients with lung cancer; AVR+CABG were performed in 1 patient with colon cancer; CABG was performed in 4 patients each with one of the following conditions: lymphoma, breast cancer, essential thrombocytosis, meningioma); and mass resection operation from the left atrium and left ventricle was performed in one patient with osteosarcoma. Results: 8 patients were discharged and 2 patients died in the early postoperative period. Postoperative left hemiparesis developed in 1 patient. 6-month, 1-year and 5-year survival rates were 79%, 37.5% and 25%, respectively. Conclusion: Open heart surgery can be successfully performed with acceptable mortality and morbidity rates on the high-risk patient group with active cancer. We believe that, where percutaneous coronary intervention and/or TAVI are not considered or deemed appropriate, surgical intervention should be performed with careful patient selection in patients with multi-vessel coronary artery disease, coronary artery stenosis +aortic stenosis, and in cases requiring double valve replacement.

Endovascular thrombectomy for acute ischemic stroke in patients with cancer: a propensity-matched analysis

BackgroundThere is a paucity of data and a belief that endovascular thrombectomy (EVT) has low efficacy for acute ischemic stroke (AIS) in patients with cancer. We aimed to critically compare the clinical outcomes of EVT for AIS in patients with and without cancer.MethodsRecords of all patients undergoing EVT for AIS between January 2015 and 2020 were screened for cancer at the time of EVT. Active cancer was defined as patients who were diagnosed with cancer and were undergoing or refused treatment for that cancer. Baseline modified Rankin Scale (mRS), age and sex were used in a 1:5 propensity score matching ratio. After matching we evaluated for any change in the National Institutes of Health Stroke Scale (NIHSS) from baseline to discharge, hemorrhagic transformation (HT), and 90-day mRS and mortality.ResultsThere were 19 patients with cancer and 95 matched controls. The mean±SD age was 70.89±11.16 years, and 17 (89.47%) were female. The baseline NIHSS was 22±7.5 and baseline mRS was 1 (IQR 1). There was no significant difference in change in baseline to discharge NIHSS, 90-day mRS or mortality; 90-day mRS 0–2 was 45.2% in the non-cancer group versus 46.7% in cancer group (p=0.54). HT was significantly higher in patients with cancer (57.89% vs 6.49%, p<0.001).ConclusionsIn propensity matched analysis of patients undergoing EVT for AIS with and without cancer, 90-day functional outcomes and mortality were similar. However, there was a significantly higher rate of HT in cancer patients.

Assessing the need for a question prompt list that encourages end-of-life discussions between patients with advanced cancer and their physicians: A focus group interview study

Objective Early integration of palliative and cancer care improves the quality of life and is facilitated by discussions about the end of life after cessation of active cancer treatment between patients with advanced cancer and their physicians. However, both patients and physicians find end-of-life discussions challenging. The aim of this study was to assess the need for a question prompt list (QPL) that encourages end-of-life discussions between patients with advanced cancer and their physicians. Methods Focus group interviews (FGIs) were conducted with 18 participants comprising 5 pancreatic cancer patients, 3 family caregivers, 4 bereaved family members, and 6 physicians. Three themes were discussed: question items that should be included in the QPL that encourages end-of-life discussions with patients, family caregivers, and physicians after cessation of active cancer treatment; when the QPL should be provided; and who should provide the QPL. Each interview was audio-recorded, and content analysis was performed. Results The following 9 categories, with 57 question items, emerged from the FGIs: (1) preparing for the end of life, (2) treatment decision-making, (3) current and future quality of life, (4) current and future symptom management, (5) information on the transition to palliative care services, (6) coping with cancer, (7) caregivers’ role, (8) psychological care, and (9) continuity of cancer care. Participants felt that the physician in charge of the patient's care and other medical staff should provide the QPL early during active cancer treatment. Significance of results Data were collected to develop a QPL that encourages end-of-life discussions between patients with advanced cancer and their physicians.